AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Plague, first described in the Old Testament, has persisted into the modern era. Plague has caused large-scale epidemics, thereby changing the course of history in many nations. The first pandemic was believed to have started in Africa and killed 100 million people over a span of 60 years. In the Middle Ages, plague killed approximately one fourth of Europe's population. The pandemic that began in China in the 1860s spread to Hong Kong in the 1890s and was subsequently spread by rats transported on ships to Africa, Asia, California, and port cities of South America. In the early twentieth century, plague epidemics accounted for about 10 million deaths in India.

Plague is worldwide in distribution, with most of the human cases reported from developing countries. This disease is an acute, contagious, febrile illness transmitted to humans by the bite of an infected rat flea. Human-to-human transmission is rare except during epidemics of pneumonic plague. The cause is the plague bacillus, a rod-shaped bacteria referred to as Yersinia pestis. Yersinia is named in honor of Alexander Yersin, who successfully isolated the bacteria in 1894 during the pandemic that began in China in the 1860s.

Pathophysiology

Domestic and urban rats are the most important reservoirs for the plague bacillus, but field mice, cats, camels, chipmunks, prairie dogs, rabbits, and squirrels can be important animal reservoirs as well. The most important vector for transmission of plague is the rat flea, Xenopsylla cheopis. Ticks and human lice have been identified as possible vectors. Humans are accidental hosts in the natural cycle of this disease.

When a rat flea ingests a blood meal from an animal infected with Y pestis, the coagulase of the bacteria causes the blood to clot. The bacilli multiply in the blood clot, and the flea inoculates thousands of these bacilli into a host's skin during subsequent blood meals. The bacilli migrate to the regional lymph nodes, are phagocytosed by the polymorphonuclear cells and mononuclear phagocytes, and multiply intracellularly. Involved lymph nodes show dense concentrations of plague bacilli, destruction of the normal architecture, and medullary necrosis. With subsequent lysis of the phagocytes, bacteremia can occur and may lead to invasion of distant organs in the absence of specific therapy.

Y pestis is a nonmotile, non–spore-forming, pleomorphic, gram-negative coccobacillus. The bacteria elaborate a lipopolysaccharide endotoxin, coagulase, and a fibrinolysin, which are the principal factors in the pathogenesis of this disease.

Frequency

United States

Approximately 10 cases of plague are reported each year from the states of Arizona, California, Colorado, New Mexico, and Utah.

In recent years, and with the potential threat for bioterrorism, the Centers for Disease Control and Prevention has specified Y pestis as a prime candidate for use in bioterrorism.

International

Most of the cases of plague reported outside of the United States are from developing countries in Africa and Asia. During 1990-1995, a total of 12,998 cases of plague were reported to the World Health Organization. The following countries reported more than 100 cases of plague: China, Congo, India, Madagascar, Mozambique, Myanmar, Peru, Tanzania, Uganda, Vietnam, and Zimbabwe. Plague outbreaks have also been reported from Malawi and Zambia.

Mortality/Morbidity

• Untreated, the mortality rate from plague can be as much as 50%.
• With appropriate antibiotics and supportive therapy, the mortality rate is reduced to 5%.

Race

In the United States, most cases occur in whites. Native Americans living in endemic areas of Arizona, New Mexico, and Utah have a 10-fold greater risk of acquiring the disease than non–Native Americans.

Sex

Males and females have been equally affected.

Age

Most cases occur in persons younger than 20 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Travel to endemic areas within and outside the United States, history of a flea bite, close contact with a potential host, or exposure to dead rodents or rabbits should heighten consideration of a plague diagnosis.

• Bubonic plague
• • Patients most commonly present with this form of plague.
  • The incubation period varies but usually lasts 2-6 days.
  • Patients have a sudden onset of high fever, chills, and headache.
  • Patients also experience body aches, extreme exhaustion, weakness, abdominal pain, and/or diarrhea.
  • Painful, swollen lymph glands (buboes) arise, usually in the groin, axilla, or neck.
• Meningeal plague
• • Fever, headache, and nuchal rigidity occur.
  • Buboes are common with meningeal plague.
  • Axillary buboes are associated with an increased incidence of the meningeal form.
• Pharyngeal plague
• • Pharyngeal plague results from ingestion of the plague bacilli.
  • Patients experience sore throat, fever, and painful cervical lymph nodes.
• Pneumonic plague
• • Pneumonic plague is highly contagious and transmitted by aerosol droplets.
  • Patients have an abrupt onset of fever and chills, accompanied by cough, chest pain, dyspnea, purulent sputum, or hemoptysis.
  • Buboes may or may not appear in pneumonic plague.
• Septicemic plague
• • Septicemic plague is observed in elderly patients and causes a rapid onset of symptoms.
  • Patients experience nausea, vomiting, abdominal pain, and diarrhea. (Diarrhea may be the predominant symptom.)
  • Patients exhibit a toxic appearance and soon become moribund.
  • Buboes are not observed with septicemic plague.
  • This form of plague is associated with a high mortality rate.

Physical

• Bubonic plague
• • Vesicles may be observed at the site of the infected flea bite. With advanced disease, pustules, carbuncles, eschar, or papules may be observed in areas of the skin drained by the involved lymph nodes. A generalized papular rash of the hands and feet may be observed.
  • Buboes are unilateral, oval, extremely tender lymph nodes and can vary from 2-10 cm in size. Femoral lymph nodes are most commonly involved. Patients with an inguinal bubo walk with a limp, and the affected limb may be in a position of flexion, abduction, and external rotation. Patients resist any attempt to examine the involved lymph nodes. Enlargement of the buboes leads to rupture and discharge of malodorous pus.
  • Hepatomegaly and splenomegaly often occur, causing tenderness.
• Pharyngeal plague causes pharyngeal erythema and painful and tender anterior cervical nodes.
• Pneumonic plague causes fever, lymphadenopathy, productive sputum, or hemoptysis.
• Septicemic plague
• • Because of an overwhelming infection with the plague bacillus, patients have a toxic appearance and may present with tachycardia, tachypnea, and hypotension. Hypothermia is common.
  • Generalized purpura may be observed and can progress to necrosis and gangrene of the distal extremities.
  • No evidence of lymphadenitis or bubo formation is apparent. Patients may die from a high level of bacteremia.

Causes

Y pestis is the cause of plague.

• Risk factors
• • Flea bite
  • Contact with a patient or a potential host
  • Contact with sick animals or rodents
  • Residing in endemic areas of plague (eg, southwestern United States)
  • Presence of a food source for rodents in the immediate vicinity of the home
  • Camping, hiking, hunting, or fishing
  • Occupational exposure (eg, researchers, veterinarians)
  • Direct handling or inhalation of contaminated tissues or tissue fluids

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Acute lymphadenitis from other causes
Acute tonsillitis
Reye syndrome

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The possibility of plague should be strongly considered in febrile patients from endemic areas who have history of exposure to rodents. Rapid recognition of the classic symptoms of this disease and laboratory confirmation is essential in order to institute lifesaving therapy.
• Expertise in testing for plague bacilli is limited to reference laboratories in plague-endemic states and the US Centers for Disease Control and Prevention (CDC).
• Leucocytosis with a predominance of neutrophils is observed, and the degree of leucocytosis is proportional to the severity of illness. Leukemoid reactions may be observed, more commonly in children.
• Peripheral blood smear shows toxic granulations and Dohle bodies.
• Thrombocytopenia is common, and levels of fibrin degradation products may be elevated.
• Serum transaminase and bilirubin levels may be elevated.
• Proteinuria may be present, and renal function test findings may be abnormal.
• Hypoglycemia may be observed.
• Blood culture results are often positive for Y pestis in patients with bubonic plague and septicemic plague. Y pestis may be observed on a peripheral blood smear.
• Lymph node aspirates often demonstrate Y pestis. In patients with pharyngeal plague, Y pestis is cultured from throat swabs.
• Cerebrospinal fluid (CSF) analysis in meningeal plague may show pleocytosis with a predominance of polymorphonuclear leukocytes. Gram stain of CSF may show plague bacilli. Limulus test of CSF demonstrates the presence of endotoxin.
• Gram stain of sputum often reveals Y pestis.

Imaging Studies

• On chest x-ray films, patchy infiltrates, consolidation, or a persistent cavity is observed in patients with pneumonic plague.
• ECG reveals sinus tachycardia and ST-T changes.
• Obtain a CT scan of the head in a patient with altered mental status.
• Nuclear imaging may help in localizing areas of lymphadenitis and meningeal inflammation.

Other Tests

• Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis.
• A passive hemagglutination test (performed on serum from a patient in acute or convalescent stages) with a 4-fold or greater increase in titer suggests plague infection.

Procedures

• Aspiration of lymph node (bubo)
• • Inject 1 mL of sterile saline into the bubo with a 20-gauge needle; after withdrawing several times, aspirate the fluid. Gram stain of the aspirate reveals gram-negative coccobacilli and polymorphonuclear leucocytes.
  • Wayson stain of the aspirate shows plague bacilli as light-blue bacilli with dark-blue polar bodies.
  • Examination of the aspirate of the fluid from the inguinal lymph nodes shows a characteristic bipolar appearance that resembles a closed safety pin.
• Lumbar puncture for CSF analysis

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Precautions
• • Place all patients thought to have plague and signs of pneumonia in strict respiratory isolation for 48-72 hours after starting antibiotic therapy.
  • Report patients thought to have plague to the local health department and to the World Health Organization.
  • Alert laboratory personnel to the possibility of the diagnosis of plague. All fluid specimens must be handled with gloves and mask to prevent aerosolization of the infected fluids.
• Supportive therapy
• • Hemodynamic monitoring and ventilatory support are performed as appropriate.
  • Intravenous fluids, epinephrine, and dopamine are implemented as necessary for correction of dehydration and hypotension.

Surgical Care

• Enlarging or fluctuant buboes require incision and drainage.

Consultations

• Infectious disease specialists
• Pulmonary and critical care specialists
• General surgeons
• Neurologists

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Streptomycin is the preferred drug of choice to treat plague. In patients who are allergic to streptomycin or who cannot tolerate streptomycin, doxycycline is a reasonable alternative.

Chloramphenicol is the preferred drug of choice in meningeal plague or for patients with hypotension. In patients with hypotension, intramuscularly administered streptomycin may be poorly absorbed.

Resistance of Y pestis to streptomycin, gentamicin, doxycycline, and chloramphenicol is very rare. No indication of emerging resistance during antibiotic therapy has been reported.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

Drug Name	Gentamicin (Garamycin)
Description	Aminoglycoside antibiotic for gram-negative coverage.
Adult Dose	2 mg/kg IV loading dose with normal renal function; then, 1.7 mg/kg IV q8h for 10 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Doxycycline (Bio-Tab, Doryx, Doxy, Vibramycin, Vibra-Tabs
Description	Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	100 mg PO/IV q12h
Pediatric Dose	<8 years: Not recommended >8 years: 2-5 mg/kg/d PO/IV qd or divided bid; not to exceed 200 mg/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Chloramphenicol (Chloromycetin)
Description	Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult Dose	500 mg PO/IV q6h
Pediatric Dose	50-75 mg/kg/d PO/IV divided q6h
Contraindications	Documented hypersensitivity
Interactions	When administered concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Transfer

• Patients with plague who are critically ill and may require transfer to another facility should be transported under strict isolation precautions.

Deterrence/Prevention

• Prophylactic antibiotic therapy
• • The CDC recommends administering prophylactic antibiotics for a short time to people who have been exposed to the bites of potentially infected rodent fleas during a plague outbreak.
  • Prophylactic antibiotic therapy is recommended for persons who have handled an animal known to be infected with the plague bacterium.
  • Prophylactic antibiotic therapy is recommended for persons who have had close exposure to a person or an animal thought to have pneumonic plague.
  • Preferred antibiotics for prophylaxis against plague are doxycycline 100 mg PO q12h for 14-21 days (for patients > 8 y) and trimethoprim 160 mg/sulfamethoxazole 800 mg PO q12h for 14-21 days.
• Plague vaccine
• • Vaccination is of limited use and is not mandatory for entry into any country.
  • The vaccine is not effective against the pneumonic form of plague.
  • Plague vaccine is recommended for field workers in areas endemic for plague and for scientists and laboratory personnel who routinely work with the plague bacterium.
• Environmental sanitation
• • Remove food sources used by rodents.
  • Make homes, buildings, or warehouses "rodent-proof."
  • Trained professionals should apply chemicals to kill fleas and rodents.
  • Trained professionals should fumigate cargo areas of ships and docks.

Complications

• Acute respiratory distress syndrome
• Chronic lymphedema from lymphatic scarring
• Disseminated intravascular coagulation
• Septic shock
• Superinfections of the buboes by Staphylococcus and Pseudomonas species

Prognosis

• Untreated patients with plague have a mortality rate of approximately 50%; however, with appropriate therapy, the mortality rate drops to approximately 5%.

Patient Education

• Report sick or dead animals to the local health department or law enforcement officials, and wear gloves when handling potentially infected animals.
• Eliminate food sources and nesting places for rodents around homes, workplaces, and recreation areas, and make homes rodent-proof.
• Personal protective measures include wearing protective clothing and applying insect repellents to clothing and skin to prevent flea bites.
• Restrain pet dogs and cats in areas endemic to plague, and regularly treat pets to control fleas.
• Spraying of appropriate chemicals by health authorities may be necessary to kill fleas at selected sites during animal plague outbreaks.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to consider the diagnosis of plague and to initiate effective antibiotic therapy
• Failure to ensure strict isolation of individuals presumed to have plague
• Failure to recognize that involvement of intra-abdominal lymph nodes in a patient with plague may mimic a surgical abdomen

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  1998 world distribution of plague. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Graph

Media file 2:  The prairie dog is a burrowing rodent of the genus Cynomys. It can harbor fleas infected with Yersinia pestis, the plague bacillus. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Photo

Media file 3:  Oriental rat flea (Xenopsylla cheopis), the primary vector of plague, engorged with blood. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 4:  Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Photo

Media file 5:  Wayson stain showing the characteristic "safety pin" appearance of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 6:  Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 7:  Histopathology of lung in fatal human plague–fibrinopurulent pneumonia. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 8:  Histopathology of lung showing pneumonia with many Yersinia pestis organisms (the plague bacillus) on a Giemsa stain. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 9:  Histopathology of spleen in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 10:  Histopathology of lymph node showing medullary necrosis and Yersinia pestis, the plague bacillus. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 11:  Histopathology of liver in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 12:  Focal hemorrhages in islet of Langerhans in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
	View Full Size Image
Media type:  Image

Media file 13:  Bioterrorist Agents. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/bioterrorism.html.
	View Full Size Image
Media type:  PDF

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Alsofrom DJ, Mettler FA, Mann JM. Radiographic manifestations of plaque in New Mexico, 1975-1980. A review of 42 proved cases. Radiology. Jun 1981;139(3):561-5. [Medline].
• Ampel NM. Plagues--what''s past is present: thoughts on the origin and history of new infectious diseases. Rev Infect Dis. Jul-Aug 1991;13(4):658-65. [Medline].
• Anderson GP, King KD, Cao LK. Quantifying serum antiplague antibody with a fiber-optic biosensor. Clin Diagn Lab Immunol. Sep 1998;5(5):609-12. [Medline].
• Ansari BM. An account of bubonic plague in seventeenth century India in an autobiography of a Mughal emperor. J Infect. Nov 1994;29(3):351-2. [Medline].
• Becker TM, Poland JD, Quan TJ. Plague meningitis--a retrospective analysis of cases reported in the United States, 1970-1979. West J Med. Nov 1987;147(5):554-7. [Medline].
• Bertherat E, Lamine KM, Formenty P. [Major pulmonary plague outbreak in a mining camp in the Democratic Republic of Congo: brutal awakening of an old scourge]. Med Trop (Mars). Nov 2005;65(6):511-4. [Medline].
• Butler T. The black death past and present. 1. Plague in the 1980s. Trans R Soc Trop Med Hyg. Jul-Aug 1989;83(4):458-60. [Medline].
• Butler T. Plague and tularemia. Pediatr Clin North Am. May 1979;26(2):355-66. [Medline].
• Campbell GL, Hughes JM. Plague in India: a new warning from an old nemesis. Ann Intern Med. Jan 15 1995;122(2):151-3. [Medline].
• Can Dis Wkly Rep. Human plague in 1990. Can Dis Wkly Rep. Nov 30 1991;17(48):266, 269-70. [Medline].
• Centers for Disease Control. From the Centers for Disease Control. Pneumonic plague--Arizona, 1992. JAMA. Oct 28 1992;268(16):2146-7. [Medline].
• Centers for Disease Control. From the Centers for Disease Control and Prevention. Detection of notifiable diseases through surveillance for imported plague--New York, September-October 1994. JAMA. Jan 18 1995;273(3):193. [Medline].
• Chanteau S, Ratsitorahina M, Rahalison L. Current epidemiology of human plague in Madagascar. Microbes Infect. Jan 2000;2(1):25-31. [Medline].
• Chanteau S, Ratsifasoamanana L, Rasoamanana B. Plague, a reemerging disease in Madagascar. Emerg Infect Dis. Jan-Mar 1998;4(1):101-4. [Medline].
• Chen TH, Elberg SS, Eisler DM. Immunity in plague: protection of the vervet (Cercopithecus aethips) against pneumonic plague by the oral administration of live attenuated Yersinia pestis. J Infect Dis. Feb 1977;135(2):289-93. [Medline].
• Chernin E. Richard Pearson Strong and the Manchurian epidemic of pneumonic plague, 1910-1911. J Hist Med Allied Sci. Jul 1989;44(3):296-319. [Medline].
• Christie AB. Plague: review of ecology. Ecol Dis. 1982;1(2-3):111-5. [Medline].
• Cleri DJ, Vernaleo JR, Lombardi LJ. Plague pneumonia disease caused by Yersinia pestis. Semin Respir Infect. Mar 1997;12(1):12-23. [Medline].
• Cohen RJ, Stockard JL. Pneumonic plague in an untreated plague-vaccinated individual. JAMA. Oct 23 1967;202(4):365-6. [Medline].
• Coleman MP. A plague epidemic in voluntary quarantine. Int J Epidemiol. Sep 1986;15(3):379-85. [Medline].
• Cook GC. Plague: past and future implications for India. Public Health. Jan 1995;109(1):7-11. [Medline].
• Coppes JB. Bubonic plague in pregnancy. J Reprod Med. Aug 1980;25(2):91-5. [Medline].
• Cramer C, Christensen B. Pneumonic plague in a 15-year-old Utah girl. J Emerg Nurs. Dec 1995;21(6):491-3. [Medline].
• Craven RB, Maupin GO, Beard ML. Reported cases of human plague infections in the United States, 1970- 1991. J Med Entomol. Jul 1993;30(4):758-61. [Medline].
• Crook LD, Tempest B. Plague. A clinical review of 27 cases. Arch Intern Med. Jun 1992;152(6):1253-6. [Medline].
• Cunha BA. Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room. Clin Microbiol Infect. Aug 2002;8(8):489-503. [Medline].
• De Backer C. [Measures taken against the plague in Diest in the fifteenth and sixteenth centuries]. Verh K Acad Geneeskd Belg. 1999;61(2):273-99. [Medline].
• Dennis DT, Hughes JM. Multidrug resistance in plague. N Engl J Med. Sep 4 1997;337(10):702-4. [Medline].
• Deodhar NS, Yemul VL, Banerjee K. Plague that never was: a review of the alleged plague outbreaks in India in 1994. J Public Health Policy. 1998;19(2):184-99. [Medline].
• Doll JM, Zeitz PS, Ettestad P. Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona. Am J Trop Med Hyg. Jul 1994;51(1):109-14. [Medline].
• Eckert EA. The retreat of plague from Central Europe, 1640-1720: a geomedical approach. Bull Hist Med. Spring 2000;74(1):1-28. [Medline].
• Ehrenkranz NJ. A. Conan Doyle, Sherlock Holmes, and murder by tropical infection. Rev Infect Dis. Jan-Feb 1987;9(1):222-5. [Medline].
• Ell SR. Immunity as a factor in the epidemiology of medieval plague. Rev Infect Dis. Nov-Dec 1984;6(6):866-79. [Medline].
• Elvin SJ, Eyles JE, Howard KA. Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine. Vaccine. Dec 21 2005;[Medline].
• Fritz CL, Dennis DT, Tipple MA. Surveillance for pneumonic plague in the United States during an international emergency: a model for control of imported emerging diseases. Emerg Infect Dis. Jan-Mar 1996;2(1):30-6. [Medline].
• Goding JR, McCracken JA, Baird DT. The study of ovarian function in the ewe by means of a vascular autotransplantation technique. J Endocrinol. Sep 1967;39(1):37-52. [Medline].
• Greenberg SJ. The "Dreadful Visitation": public health and public awareness in seventeenth-century London. Bull Med Libr Assoc. Oct 1997;85(4):391-401. [Medline].
• Gushulak BD, St John R, Jeychandran T. Human plague in India, August-October, 1994. Can Commun Dis Rep. Oct 30 1994;20(20):181-3. [Medline].
• Henderson RJ. Summary of recent abstracts. VI. Plague. Trop Dis Bull. Jul 1973;70(7):601-7. [Medline].
• Henderson RJ. Plague. Trop Dis Bull. Jul 1969;66(7):653-9. [Medline].
• Hinnebusch BJ. Bubonic plague: a molecular genetic case history of the emergence of an infectious disease. J Mol Med. Sep 1997;75(9):645-52. [Medline].
• Hoffman SL. Plague in the United States: the "black death" is still alive. Ann Emerg Med. Jun 1980;9(6):319-22. [Medline].
• Houston JB, Carlile DJ. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev. Nov 1997;29(4):891-922. [Medline].
• Hull HF, Montes JM, Mann JM. Septicemic plague in New Mexico. J Infect Dis. Jan 1987;155(1):113-8. [Medline].
• Inglesby TV, Dennis DT, Henderson DA. Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. May 3 2000;283(17):2281-90. [Medline].
• Isaacson M, Qhobela QM, Davis DH. Serological studies on human plague in Southern Africa. Part II. A bubonic/pneumonic plague epidemic in Lesotho. S Afr Med J. Jun 5 1976;50(24):929-32. [Medline].
• Isaacson M, Hallett AF. Serological studies on human plague in Southern Africa. Part I. Plague antibody levels in a population during a quiescent and a subsequent active period in an endemic region. S Afr Med J. Jul 12 1975;49(29):1165-8. [Medline].
• Jefferson T, Demicheli V, Pratt M. Vaccines for preventing plague. Cochrane Database Syst Rev. 2000;(2):CD000976. [Medline].
• John TJ. Emerging & re-emerging bacterial pathogens in India. Indian J Med Res. Jan 1996;103:4-18. [Medline].
• Jones AM, Mann J, Braziel R. Human plague in New Mexico: report of three autopsied cases. J Forensic Sci. Jan 1979;24(1):26-38. [Medline].
• Josko D. Yersinia pestis: still a plague in the 21st century. Clin Lab Sci. Winter 2004;17(1):25-9. [Medline].
• Kaufmann AF, Boyce JM, Martone WJ. From the Center for Disease Control. Trends in human plague in the United States. J Infect Dis. Apr 1980;141(4):522-4. [Medline].
• Kilonzo BS. Plague epidemiology and control in eastern and southern Africa during the period 1978 to 1997. Cent Afr J Med. Mar 1999;45(3):70-6. [Medline].
• Koornhof HJ, Smego RA, Nicol M. Yersiniosis. II: The pathogenesis of Yersinia infections. Eur J Clin Microbiol Infect Dis. Feb 1999;18(2):87-112. [Medline].
• Lyamuya EF, Nyanda P, Mohammedali H. Laboratory studies on Yersinia pestis during the 1991 outbreak of plague in Lushoto, Tanzania. J Trop Med Hyg. Oct 1992;95(5):335-8. [Medline].
• MMWR. Detection of notifiable diseases through surveillance for imported plague--New York, September-October 1994. Morb Mortal Wkly Rep. Nov 11 1994;43(44):805-7. [Medline].
• MMWR. Pneumonic plague--Arizona, 1992. MMWR Morb Mortal Wkly Rep. Oct 9 1992;41(40):737-9. [Medline].
• MMWR. Fatal human plague--Arizona and Colorado, 1996. MMWR Morb Mortal Wkly Rep. Jul 11 1997;46(27):617-20. [Medline].
• MMWR. Prevention of plague: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. Dec 13 1996;45(RR-14):1-15. [Medline].
• MMWR. Human plague--United States, 1993-1994. MMWR Morb Mortal Wkly Rep. Apr 8 1994;43(13):242-6. [Medline].
• MMWR. Pneumonic plague--Arizona, 1992. MMWR Morb Mortal Wkly Rep. Oct 9 1992;41(40):737-9. [Medline].
• MMWR. Plague--United States, 1992. MMWR Morb Mortal Wkly Rep. Oct 23 1992;41(42):787-90. [Medline].
• MMWR. Imported bubonic plague--District of Columbia. MMWR Morb Mortal Wkly Rep. Dec 14 1990;39(49):895, 901. [Medline].
• Madon MB, Hitchcock JC, Davis RM. An overview of plague in the United States and a report of investigations of two human cases in Kern county, California, 1995. J Vector Ecol. Jun 1997;22(1):77-82. [Medline].
• Mann JM, Shandler L, Cushing AH. Pediatric plague. Pediatrics. Jun 1982;69(6):762-7. [Medline].
• Mann JM, Schmid GP, Stoesz PA. Peripatetic plague. JAMA. Jan 1 1982;247(1):47-8. [Medline].
• Mann JM, Martone WJ, Boyce JM. Endemic human plague in New Mexico: risk factors associated with infection. J Infect Dis. Sep 1979;140(3):397-401. [Medline].
• McClean KL. An outbreak of plague in northwestern province, Zambia. Clin Infect Dis. Sep 1995;21(3):650-2. [Medline].
• McEvedy C. The bubonic plague. Sci Am. Feb 1988;258(2):118-23. [Medline].
• Meyer KF, Cavanaugh DC, Bartelloni PJ. Plague immunization. I. Past and present trends. J Infect Dis. May 1974;129:Suppl:S13-8. [Medline].
• Mittal V, Rana UV, Jain SK. Quick control of bubonic plague outbreak in Uttar Kashi, India. J Commun Dis. Dec 2004;36(4):233-9. [Medline].
• Moreno AJ, Reeves TA, Rodriguez AA. Imaging in plague. Eur J Nucl Med. 1987;13(6):315-7. [Medline].
• Morris JT, McAllister CK. Bubonic plague. South Med J. Mar 1992;85(3):326-7. [Medline].
• Mudur G. India''s pneumonic plague outbreak continues to baffle. BMJ. Sep 16 1995;311(7007):706. [Medline].
• Mwengee W, Butler T, Mgema S. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis. Mar 1 2006;42(5):614-21. [Medline].
• Oeding P. [The black death in Norway]. Tidsskr Nor Laegeforen. Jun 30 1990;110(17):2204-8. [Medline].
• Parmenter RR, Yadav EP, Parmenter CA. Incidence of plague associated with increased winter-spring precipitation in New Mexico. Am J Trop Med Hyg. Nov 1999;61(5):814-21. [Medline].
• Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. Jan 1997;10(1):35-66. [Medline].
• Poos LR. Plague mortality and demographic depression in later medieval England. Yale J Biol Med. May-Jun 1981;54(3):227-34. [Medline].
• Rahalison L, Vololonirina E, Ratsitorahina M. Diagnosis of bubonic plague by PCR in Madagascar under field conditions. J Clin Microbiol. Jan 2000;38(1):260-3. [Medline].
• Ratsitorahina M, Chanteau S, Rahalison L. Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in Madagascar. Lancet. Jan 8 2000;355(9198):111-3. [Medline].
• Ratsitorahina M, Rabarijaona L, Chanteau S. Seroepidemiology of human plague in the Madagascar highlands. Trop Med Int Health. Feb 2000;5(2):94-8. [Medline].
• Reed WP, Palmer DL, Williams RC. Bubonic plague in the Southwestern United States. A review of recent experience. Medicine (Baltimore). Nov 1970;49(6):465-86. [Medline].
• Reeder MM, Palmer PE. Acute tropical pneumonias. Semin Roentgenol. Jan 1980;15(1):35-49. [Medline].
• Risse GB. "A long pull, a strong pull, and all together": San Francisco and bubonic plague, 1907-1908. Bull Hist Med. Summer 1992;66(2):260-86. [Medline].
• Russell P, Eley SM, Green M. Efficacy of doxycycline and ciprofloxacin against experimental Yersinia pestis infection. J Antimicrob Chemother. Feb 1998;41(2):301-5. [Medline].
• Russell P, Nelson M, Whittington D. Laboratory diagnosis of plague. Br J Biomed Sci. Dec 1997;54(4):231-6. [Medline].
• Shangula K. Successful plague control in Namibia. S Afr Med J. Nov 1998;88(11):1428-30. [Medline].
• Shivaji S, Bhanu NV, Aggarwal RK. Identification of Yersinia pestis as the causative organism of plague in India as determined by 16S rDNA sequencing and RAPD-based genomic fingerprinting. FEMS Microbiol Lett. Aug 15 2000;189(2):247-52. [Medline].
• Sloan AW. The Black Death in England. S Afr Med J. Apr 25 1981;59(18):646-50. [Medline].
• Smego RA, Frean J, Koornhof HJ. Yersiniosis I: microbiological and clinicoepidemiological aspects of plague and non-plague Yersinia infections. Eur J Clin Microbiol Infect Dis. Jan 1999;18(1):1-15. [Medline].
• Solomon T. Alexandre Yersin and the plague bacillus. J Trop Med Hyg. Jun 1995;98(3):209-12. [Medline].
• Suntsov VV, Huong LT, Suntsova NI. Plague foci in Viet Nam: zoological and parasitological aspects. Bull World Health Organ. 1997;75(2):117-23. [Medline].
• Titball RW, Leary SE. Plague. Br Med Bull. 1998;54(3):625-33. [Medline].
• Tomich PQ, Barnes AM, Devick WS. Evidence for the extinction of plague in Hawaii. Am J Epidemiol. Feb 1984;119(2):261-73. [Medline].
• Trong P, Nhu TQ, Marshall JD. A mixed pneumonic bubonic plague outbreak in Vietnam. Mil Med. Feb 1967;132(2):93-7. [Medline].
• Velimirovic B. Plague and Glasnost. First information about human cases in the USSR in 1989 and 1990. Infection. Nov-Dec 1990;18(6):388-93. [Medline].
• Velimirovic B. Plague in South-East Asia. A brief historical summary and present geographical distribution. Trans R Soc Trop Med Hyg. 1972;66(3):479-504. [Medline].
• Viseltear AJ. The pneumonic plague epidemic of 1924 in Los Angeles. Yale J Biol Med. Mar 1974;47(1):40-54. [Medline].
• Washington RL, Barkin RM, Hillman JR. Septicemic plague that mimics Reye''s syndrome. Am J Dis Child. Apr 1979;133(4):434-5. [Medline].
• Welty TK. Plague. Am Fam Physician. Jun 1986;33(6):159-64. [Medline].
• White ME, Gordon D, Poland JD. Recommendations for the control of Yersinia pestis infections. Recommendations from the CDC. Infect Control. Sep-Oct 1980;1(5):324-9. [Medline].
• Wilson ME. The power of plague. Epidemiology. Jul 1995;6(4):458-60. [Medline].
• Wilson WR. Antimicrobial chemoprophylaxis. Med Clin North Am. Jan 1983;67(1):99-112. [Medline].
• Wkly Epidemiol Rec. Human plague in 1997. Wkly Epidemiol Rec. Oct 15 1999;74(41):340-4. [Medline].
• Wkly Epidemiol Rec. Human plague in 1996. Wkly Epidemiol Rec. Nov 20 1998;73(47):366-9. [Medline].
• Wkly Epidemiol Rec. Epidemic of plague. Wkly Epidemiol Rec. Oct 16 1992;67(42):315-6. [Medline].
• Wkly Epidemiol Rec. Plague. Wkly Epidemiol Rec. Mar 16 1990;65(11):83-4. [Medline].
• Yom SS. Plague and AIDS in literature. JAMA. Feb 5 1997;277(5):437-8. [Medline].
• Yule WL. A Scottish doctor''s association with the discovery of the plague bacillus. Scott Med J. Dec 1995;40(6):184-6. [Medline].
• von Reyn CF, Weber NS, Tempest B. Epidemiologic and clinical features of an outbreak of bubonic plague in New Mexico. J Infect Dis. Oct 1977;136(4):489-94. [Medline].
• von Reyn CF, Barnes AM, Weber NS. Bubonic plague from exposure to a rabbit: a documented case, and a review of rabbit-associated plague cases in the United States. Am J Epidemiol. Jul 1976;104(1):81-7. [Medline].

Article Last Updated: May 12, 2006